Alprazolam versus imipramine in depressed out-patients with neurovegetative signs

The purpose of this study was to compare the safety and efficacy of a relatively new antidepressant drug, alprazolam (a triazolobenzodiazepine) with imipramine in the treatment of 60 depressed symptomatic volunteers. Eligible patients were randomly assigned after a 1-week washout to one of the medications and followed for 6 treatment weeks. Contrary to the earlier report of Feighner et al. (1983), who found alprazolam superior to imipramine and placebo, but consistent with Rush et al. (1985) we find imipramine superior in efficacy to alprazolam on a variety of symptoms. Both the present study and Rush's study employed patients with signs indicative of response to tricyclics. Feighner's patients may have been the type who tend to be less responsive to tricyclics but may be more responsive to alprazolam. Some of our data also show that alprazolam may have a more advantageous effect in the early weeks of treatment but is overtaken in subsequent treatment weeks by imipramine.     

Clomipramine for panic disorder: I. The first 10 weeks of a long-term comparison with imipramine

Clomipramine and imipramine treatments were compared in a sample of 152 panic disorders. Diagnosis was according to the positive criteria of DSM-III-R, but without exclusion of comorbid affective or personality disorders. The 2-year design provides non-blind treatment under typical clinical practice conditions, and it includes random assignment, periodic assessment with standardized measures, and comparable, flexible drug dosages. Findings on six outcome measures in the first 59 cases to complete 10 weeks showed both tricyclics to be markedly and equally effective for blocking panic attacks, alleviating phobic avoidance, and reducing nonspecific aspects of anxiety. Clomipramine's predominantly serotonergic action seemed not to determine a different action spectrum. During the first 2 weeks, clomipramine was significantly and unexpectedly superior to imipramine in both antipanic and antiphobic actions. These results require replication under double-blind conditions.     

Secondary depression in panic disorder and agoraphobia. II. Dimensions of depressive symptomatology and their response to treatment

Secondary depressive symptomatology in 435 subjects with panic disorder and phobic avoidance was studied before and after alprazolam treatment. No subject who had a primary affective disorder was included. Calculation of Hamilton Depression Rating Scale factor scores revealed that the agitation/anxiety, sleep disturbance, and somatization factors accounted for approximately 75% of the HAM-D total score; these all showed significant improvement with alprazolam treatment. There were few differences in dimensions of depressive symptomatology between those subjects with and those without major depression; the main difference was in the overall intensity of the depression.     

Response of panic disorder to fixed doses of alprazolam or imipramine

This paper reports the results of a double-blind comparison of fixed daily doses of 6 mg of alprazolam, 2 mg of alprazolam, 225 mg of imipramine, and placebo for 8 weeks in 81 patients who met DSM-III criteria for panic disorder with or without agoraphobia. Final scores on eight clinical measures were analyzed from all patients who entered the study and from the subset who completed at least 4 weeks of treatment. Eighty-six percent of the high-dose alprazolam patients completed the study. Only 50% of the imipramine patients completed 8 weeks of treatment, apparently because of activation early in treatment and slow onset of therapeutic effects. This study confirmed the therapeutic effectiveness and safety of alprazolam, especially at the higher dose, in panic disorder. It also confirmed the therapeutic effectiveness of imipramine among patients who tolerated the drug. It suggested the usefulness of a flexible, individual approach to dose escalation with imipramine. Methodologically the study underscored the importance of using multiple approaches to the analysis of clinical data from therapeutic trials of psychotropic agents with complex effects that may contribute to patients' premature termination.     

How "blind" are double-blind studies?

Psychopharmacological studies usually attempt to eliminate "nonspecific" influences on outcome by double-blind designs. In a randomized, double-blind comparison of alprazolam, imipramine, and placebo, the great majority of panic disorder patients (N = 59) and their physicians were able to rate accurately whether active drug or placebo had been given. Moreover, physicians could distinguish between the two types of active drugs. Inasmuch as correct rating was possible halfway through treatment, concerns about the internal validity of the double-blind strategy arise.     

Desipramine treatment in panic disorder.

Apart from imipramine (IMI), the efficacy of tricyclic antidepressants in panic disorder (PD) has received surprisingly little investigation. The authors report on a 6 week open trial of desipramine (DMI) preceded by a 10 day placebo lead-in, in 15 patients with PD. By week 6, 80% of the patients were globally rated as much or very much improved on a mean dose of 198 mg. Much of the improvement resulted from a reduction in non-panic attack symptomatology (i.e., psychic, somatic and phobic anxiety). Longer duration of illness, male gender and residual psychic anxiety were associated with poorer response in a subgroup of patients. DMI caused minimal intolerable side effects, suggesting possible compliance advantages in comparison to IMI. Beyond supporting the efficacy of DMI in PD, the results of the study point to a significant medication responsive non-panic illness component and caution against over-relying on panic attacks in assessing both illness severity and treatment response.     

A comparison of alprazolam and behavior therapy in treatment of panic disorder

The results of a clinical outcome study (N = 57) comparing behavior therapy directed at panic disorder (panic control treatment [PCT]) with alprazolam were reported. These conditions were compared with a medication placebo and a waiting-list control group. Patterns of results on measures of panic attacks, generalized anxiety, and global clinical ratings reveal that PCT was significantly more effective than placebo and waiting-list conditions on most measures. The alprazolam group differed significantly from neither PCT nor placebo. The percentage of clients completing the study who were free of panic attacks following PCT was 87%, compared with 50% for alprazolam, 36% for placebo, and 33% for the waiting-list group. Since alprazolam may work more quickly than PCT but may also interfere with the effects of behavioral treatment, these data suggest a series of studies on the feasibility of integrating these treatments and on the precise patterns and mechanisms of action of various successful treatment approaches to panic disorder.     

Triazolobenzodiazepines Exert Immunopotentiating Activities on Normal Human Peripheral Blood Lymphocytes

Previous studies have demonstrated that benzodiazepines (BDZ) (e.g. diazepam) inhibit immune responsiveness. Since these drugs are largely used in psychiatric patients it is of great importance to verify the existence of different types of BDZ, which are not suppressive for the immune system. In this framework, our results indicate that alprazolam and triazolam, two triazolo-BDZ, do not modify in vitro phagocytosis and killing exerted by normal human polimorphonuclear cells and monocytes. On the contrary, they significantly enhance T lymphocyte-dependent antibacterial activity in normal donors. These data support the concept that triazolo-BDZ and, in particular, alprazolam may represent more appropriate drugs for the treatment of psychiatric patients (e.g. patients with phobic disorders and/or migraine) who display immunodeficits.     

Triazolobenzodiazepines Exert Immunopotentiating Activities on Normal Human Peripheral Blood Lymphocytes

Abstract

Previous studies have demonstrated that benzodiazepines (BDZ) (e.g. diazepam) inhibit immune responsiveness. Since these drugs are largely used in psychiatric patients it is of great importance to verify the existence of different types of BDZ, which are not suppressive for the immune system. In this framework, our results indicate that alprazolam and triazolam, two triazolo-BDZ, do not modify in vitro phagocytosis and killing exerted by normal human polimorphonuclear cells and monocytes. On the contrary, they significantly enhance T lymphocyte-dependent antibacterial activity in normal donors. These data support the concept that triazolo-BDZ and, in particular, alprazolam may represent more appropriate drugs for the treatment of psychiatric patients (e.g. patients with phobic disorders and/or migraine) who display immunodeficits.     

Disappearance of memory deficits in outpatient depressives responding to imipramine

We evaluated learning and memory in 50 depressed patients prior to and following 4 week treatment with imipramine compared to 21 normal controls tested at corresponding times. At baseline, the depressives did worse than normals on most memory tasks with the difficult memory tasks, regardless of store, modality or type of task best distinguishing between depressive and normal memory. Following imipramine treatment, responders performed better than nonresponders on the difficult memory tasks, and not significantly differently from controls on most tasks. This, as well as the fact that the responders improved to a greater degree than controls on most measures (in a few cases the difference was statistically significant) and the fact that at 4 weeks complete responders to imipramine did significantly better than partial responders to imipramine, indicates that relief from depression is highly related to improved memory functioning. The finding that complete responders to imipramine were not significantly worse than normal controls suggests that imipramine did not have significant adverse effects on memory.     

Ambivalence in coping with dental fear and avoidance: a qualitative study

Dental phobia is a widespread problem, which can have significant impact on the individual's health and daily life. This grounded theory study aims to explore the situation of dental phobic patients: how dental phobia interferes with their normal routines and functioning, social activities and relationships, what factors contribute to the maintenance of dental fear and how they cope with their fear. In the qualitative analysis of thematized in-depth interviews four main categories were developed: threat to self-respect and well-being, avoidance, readiness to act and ambivalence in coping. The results show that several psychological and social factors interact in determining how dental phobic individuals cope with their fear, and demonstrate in what way dental fear affects their daily lives.     

Clinical and electromyographic characteristics of tremor in patients with generalized anxiety disorder

The tremor in patients with anxiety was supposed to be an enhanced physiological tremor. However no detailed clinical and electromyographic examination of tremor in patients with anxiety has been published. It has been also supposed that propranolol or benzodiazepines may influence the tremor The aim of this investigation was to establish the clinical and electromyographic pattern of tremor in patients with anxiety and to compare the effects of propranolol and alprazolam treatment. One hundred and twenty patients with tremor and generalized anxiety disorder were investigated. Tremor was scored clinically by the Webster Tremor Scale. Electromyographic examination of tremor activity from antagonistic hand muscles was performed. Sixty patients were treated with alprazolam and propranolol, in an open, crossover design, while the other sixty patients received no particular treatment for the tremor The patients were randomly assigned to treatment with propranolol, alprazolam, or received no tremor treatment. Our results revealed a postural and kinetic tremor with characteristics of an enhanced physiological tremor. Tremor involved only upper limbs and no other body parts. Treatment with propranolol or alprazolam had similar favorable effect on tremor. In conclusion tremor in generalized anxiety disorder is an enhanced physiological tremor The kinetic tremor disturbs patients and particular tremor treatment with propranolol or alprazolam should be applied.     

Treatment of mood-congruent psychotic depression with imipramine

BACKGROUND: Most studies report a poor response of psychotic depressed patients to treatment with a tricyclic antidepressant alone compared to combined treatment with an antipsychotic preparation and compared to non-psychotic depressed patients. However, the issue of optimal treatment of psychotic depressed patients has not been resolved as yet. Previously, we reported a significant difference in response to mirtazapine compared to imipramine in a randomised, double-blind, fixed-blood-level study with in-patients with major depression. In the current study we focus on the treatment response to imipramine in a group of patients with psychotic depression and compare this to patients who manifest no psychotic features. Our aim in presenting these findings was to contribute to the discussion on the optimal treatment of psychotic depressed patients. METHODS: Fifty-two patients with a unipolar major depression (DSM-IIIR), comprising 15 patients with mood-congruent psychotic features and 37 patients with no psychotic features, were commenced on treatment with imipramine after a drug-free and placebo-washout period of 7 days. The dose of imipramine was adjusted for all patients to a predetermined blood level. The Hamilton (HRSD) and Montgomery-Asberg (MADRS) Depression Rating Scales were used to evaluate treatment response. RESULTS: Of the 45 patients who completed the study, nine of the 13 psychotic patients (69.2%) and 14 of the 32 non-psychotic patients (43.8%) responded to treatment. The patients with psychotic features demonstrated a lower mean final HRSD score, together with a greater fall in MADRS score over time, compared to the non-psychotic group. Both these findings remained statistically significant after controlling for a number of possible confounding factors. CONCLUSIONS: These results demonstrate that, in this group of patients with mood-congruent psychotic depression, imipramine used on its own together with strict control of serum drug levels produced a high treatment response rate of 70%. CLINICAL IMPLICATIONS: If replicated, these findings suggest that imipramine with control of blood levels of medication may be a useful first-line treatment for depressed patients with mood-congruent psychotic features. LIMITATIONS: Our sample size was modest. This fact may caution against generalisation of the results.     

Follow-up study of patients with panic disorder and agoraphobia with panic attacks treated with tricyclic antidepressants

One hundred and seven patients with panic disorder or agoraphobia with panic attacks were studied 1-4 years after treatment with a tricyclic antidepressant. At follow-up more than 80% of the patients remained symptomatic but fewer than half were experiencing panic attacks and only 40% were avoiding phobic situations. Although patients with agoraphobia were more severely ill and had been ill longer than those with panic disorder, their response to tricyclics and eventual outcome was similar to that for patients with panic disorder. Panic and agoraphobic patients who had the most severe symptoms initially showed the least improvement. The results suggest that panic disorder and agoraphobia with panic attacks are variants of a single illness and that, despite its chronicity, this illness has a favorable outcome.     

Treatment of post-traumatic stress disorder with imipramine

The patient with post-traumatic stress disorder (PTSD) may be incapacitated by anxiety, sleep disturbances, and other difficulties. Ten patients with PTSD received imipramine for two to three weeks and, at the end of the study, reported significantly decreased severity of intrusion items such as forced recollections, and sleep and dream disturbances, along with cessation of flashbacks in three of four patients with them. Most avoidance items did not decrease noticeably in severity. Imipramine, in combination with psychotherapy, may be an effective treatment strategy for patients with PTSD. Double-blind investigations are warranted.     

A randomised,double-blind comparison of milnacipran and imipramine in the treatment of depression

This multicentre, double-blind, randomised trial in 109 patients compared the efficacy and tolerance of the novel selective serotonin and noradrenaline reuptake inhibitor (SNRI) antidepressant milnacipran (50 mg twice daily, n=53) with the established tricyclic agent imipramine (75 mg twice daily, n=56) over a period of 6 weeks, in patients with major depression (Montgomery-Asberg depression rating score (MADRS) > or =25). Initiation of antidepressant medication was conducted during a 2-week period of hospitalisation, after a 3- to 7-day washout period. Concomitant psychiatric medication was limited to lorazepam, cyamemazine, chloral hydrate and long-term uncomplicated lithium therapy. Assessment for efficacy using the MADRS and Hamilton rating scales of depression, a visual analogue scale and global evaluation revealed both agents to be highly effective (P=0.0001) in this group of patients. Milnacipran was found to be of similar efficacy to imipramine. Tolerance, assessed by physiological and biochemical examinations with routine inventory and spontaneous report of adverse events, revealed a clear advantage for milnacipran. The incidence of anticholinergic events with milnacipran was about half that with imipramine and the overall incidence of adverse events by either reporting method was markedly lower with milnacipran than with imipramine. Furthermore, the patient drop-out rate with imipramine was double that experienced with milnacipran. Milnacipran appears to possess equal antidepressant efficacy to imipramine but with markedly superior tolerance. Therefore, milnacipran constitutes an important new treatment option in major depression.     

Panic disorder, agoraphobia, and anxiety-relevant cognitive style

We attempted to identify factors differentiating Agoraphobia with Panic Attacks (AG) from Panic Disorder (PD) patients. Twenty-three AG and 27 PD patients were compared. No significant difference in severity of illness was found. As predicted, the groups differed on a measure of anxiety-relevant cognitions developed for this study, the Anxious Thoughts and Tendencies scale (AT&T) (P less than 0.02). We suggest that differences in interpretation of panic attacks account for the development of of phobic avoidance behavior in some but not all PD patients. The intercorrelations among measures suggest that Panic Disorder may be conceptualized as having several independent although related components (panic attacks, general anxiety, phobic anxiety, and cognitive distortions).     

Prediction of response of chronic depression to imipramine

We had previously reported that imipramine was superior to placebo for the treatment of chronic depression. As a part of that study, we subsequently investigated clinical and demographic variables which might be associated with favorable or poor outcome for treatment with imipramine or placebo. Results are reported herein. Eight-six patients were entered and 53 completed an 8-week protocol. Outcome was assessed based on a 6-week, double-blind treatment phase, which followed a 2-week, single-blind placebo phase. Outcome was not found to significantly relate to demographic variables, severity or course of depression, diagnostic subtype, symptom profile, or DST results. Some modest associations were found between 'neurotic' personality traits and poor outcome. Results are discussed and compared with prior studies of prediction of tricyclic antidepressant response in both acute and chronic depressions.     

利培酮合并阿普唑仑治疗急性期精神分裂症的对照分析

目的以氯氮平作对照,观察分析利培酮合并阿普唑仑治疗精神分裂症急性兴奋的疗效和副反应.方法将符合CCMD-3诊断标准的精神分裂症,随机分为利培酮合并阿普唑仑组和氯氮平组,观察4周,分别于治疗前、治疗后第4天、第7天、第14天、第28天评定PANSS量表总分、兴奋因子分（P4、P7、G8、G14）及TESS评定副反应.结果在治疗4天后,利培酮合并阿普唑仑组和氯氮平组兴奋因子均显著下降,但两组之间无显著性差异;28天时利培酮组PANSS总分高于氯氮平组,利培酮长期疗效优于氯氮平.氯氮平组嗜睡、便秘、流涎、心动过速高于利培酮组.结论利培酮合并阿普唑仑对治疗精神分裂症急性期兴奋与氯氮平组疗效相当,效果好,不良反应较氯氮平组轻,安全性好,病人易接受.     

The Baby Makers: An In-Depth Single-Case Study of Conscious and Unconscious Psychological Reactions to Infertility and 'Baby-Making' Technology

ABSTRACT. Recent innovations of interventive technologies of fertilisation (AIH, AID, IVF) have brought in their wake a wave of psychological reactions in the consumers. This new syndrome includes psychological symptoms such as derealisation, depersonalisation, hypochondria, low self-esteem, guilt and neurotic depression; anxiety reactions; phobic avoidance and obsessional reactions with rumination and compulsive rituals. In addition, considerable interpersonal stress is manifested within the marital/intimate relationships of these patients who strive to 'make' a baby, rather than being able to just naturally 'have' one.
This presentation focuses on unconscious phantasies and dynamic processes underlying such symptomatology, including the emotional effects of being unable to treat intercourse as a twoperson generative event or the body as a creative fertile exponent of the self. Data is drawn from an in-depth study of 19 patients seen in 1–5 per week psychoanalysis or individual/couple therapy and a single case is presented in depth. Attention is focused on subfertile patients' special transference relationship to the medical specialist - as 'Baby Maker'.